Aravind Asokan
Duke University, NC·Biomedical Engineering
Gene therapy treats inherited disease by delivering a working copy of a gene into a patient's cells. One of the leading delivery vehicles is adeno-associated virus (AAV), a small virus whose protein shell, the capsid, can be loaded with a therapeutic gene instead of viral genes.
- Fields
Biomedical Engineering
Microbiology & Immunology
Genetics
- Topics
adeno-associated virus
gene therapy
viral vectors
- Grants
- 3 known grants, through Jul 2029
What they work on
- Test whether IceMG, an engineered protease that cleaves human and monkey IgG and IgM antibodies, blocks complement activation and modulates B-cell signaling, using human cell models, humanized mice and non-human primates.
- Engineer and characterize next-generation immunomodulatory proteins (IceRx) aimed at clinical translation for patients who already carry antibodies against AAV capsids.
- Determine whether the membrane-associated accessory protein MAAP, encoded by a frameshifted reading frame in the AAV cap gene, acts as an exit factor across different AAV clades.
- Define the molecular mechanism by which MAAP taps host secretory pathways to drive AAV release and exosome production, and engineer MAAP variants plus stable producer cell lines that secrete more vector.
- Map multiple traits of cross-species compatible AAV variants (ccAAVs) and related mutants, including tissue tropism, transduction, epigenetics, transcription and immunogenicity, in normal mice, CRISPR editor mice and rhesus macaques.
- Test the idea that the AAV capsid itself dictates the epigenetic state and transcriptional activity of the delivered vector genome across species, to derive design rules for lower-dose vectors.
More about the research
Six AAV-based therapies have been approved by the FDA, but two obstacles keep recurring: the immune system reacts to the capsid, and very large doses are needed, which strains manufacturing and raises toxicity risk. Work here attacks both obstacles, by designing proteins that temporarily blunt the antibody response, by studying how AAV leaves a producer cell so manufacturing can be made cleaner, and by dissecting why some capsids deliver genes far more efficiently than others across species.
Why it matters
AAV gene therapies already treat eye, neuromuscular and metabolic disorders, but immune reactions and very high required doses limit who can be treated and how safely. Reagents such as IceMG could make it possible to dose patients who already carry anti-AAV antibodies and to reduce complement-driven toxicities, with possible extensions to autoimmune disease and organ transplantation. Improved secretion-based manufacturing could raise vector yield and purity, and capsids that work at lower doses could improve both efficacy and safety.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
George Aslanidi
University of Minnesota, MN·Microbiology & Immunology
Test in non-human primates whether extracellular-vesicle-associated AAV vectors deliver genes efficiently to the airway lining, combining non-invasive live imaging of gene expression with post-necropsy analysis of transduced cell subpopulations.
Arun Srivastava
University of Florida, FL·Medicine & Clinical Research
Develop liver-de-targeted, capsid- and genome-modified next-generation AAV vectors based on AAVrh74 for skeletal muscle and AAV9 for the central nervous system, and demonstrate enhanced expression from AAV-PDHA1 vectors.
Matthew Gardner
Emory University, GA·Microbiology & Immunology
Test whether co-delivering an AAV vector encoding rhesus macaque PD-L1, a protein that engages the T-cell brake receptor PD-1, sustains blood levels of the HIV broadly neutralizing antibody 10-1074 high enough to protect macaques from repeated low-dose SHIV challenge.
The school
Duke University: 61 labs on PI Pages, $1.6B a year on research, 417 research doctorates a year.
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